Situated in Mainz, Germany, the Institute of Molecular Biology gGmbH (IMB) attracted a truly international research community during the third annual IMB conference on 4-7 June 2015. Funded by the Boehringer Ingelheim Foundation, the non-profit company conducts basic and applied research in the fields of developmental biology, epigenetics, genome stability and related biomedical areas.
This years’ IMB conference program focused on DNA repair mechanisms and related chromatin dynamics. For everyone interested in DNA damage response (DDR) signaling or genome stability, this was definitely the place to be for one weekend. Twenty-eight excellent speakers presented attractive fundamental science findings to more than 150 colleagues. The conference was framed by two outstanding keynote lectures by Susan Gasser and Titia K. Sixma, and organized in four well-compiled sessions dealing with:
- DNA Damage Signaling and Checkpoint Activation in Chromatin
- Influence of Chromatin on Damage Processing and Repair
- Replication of Chromatin in the Presence of DNA Damage
- Chromatin Dynamics and Remodeling in Response to DNA Damage.
A range of topics from ATM (ataxia telangiectasia mutated – the no.1 regulator of DDR) to cell cycle status importance and Zinc-finger mutations in immunodeficiency was covered. Every talk seemed to add more information to one big picture, revealing the beauty of science and molecular biology. The conference attendees especially valued the interesting and dynamic discussions that accompanied talks and poster sessions.
The role of non-coding RNA in the control of DNA damage response
Fabrizio d’Adda di Fagagna, IFOM, Milan, Italy and IGM-CNR, Pavia, Italy
The d’Adda di Fagagna lab is best known for their studies on DNA Damage Response (DDR) and cellular senescence. As pioneers in the field, they are also trying to understand the role of non-coding RNAs in DDR signaling. In contrast to the widespread believe DNA damage inhibits transcription, they discovered a new class of DNA damage-response RNAs (DDRNAs) that are actively transcribed at DNA lesion sites. After DICER- and DROSHA-dependent processing, these 20-35 nt-long RNAs act in cis to promote DDR foci formation as demonstrated by in vitro studies. The sequence-specific action of DDRNAs offers novel possibilities to study and target the DDR regulatory machinery, which was so far mainly thought to be protein-dependent.
DNA damage in development and aging: Organismal adaptations to genome instability
Björn Schumacher, University and CEACAD, Cologne, Germany
Defects in genome maintenance mechanisms can lead to severe phenotypes characterized by developmental failures, premature aging and increased cancer susceptibility. The Schumacher lab investigates systemic stress responses towards DNA damage at the interplay of somatic tissues and germ line cells.
In order to secure successful reproduction, somatic tissues show enhanced tolerance to DNA damage and promote development until the germ line genome is repaired. Focusing on the nucleotide excision repair (NER) pathway, which is conserved from man to C. elegans, the lab identified the FOXO transcription factor DAF-16 as a key regulator to promote DNA damage persistence in somatic tissues. DAF-16 activity declines with age in worms and could therefore account for DNA-damage driven tissue degeneration with aging, also in humans.
Chromatin dynamics and nuclear subcompartments in DNA double strand break repair
Susan Gasser, Friedrich Miescher Institute, Basel, Switzerland
In order to repair a DNA double-strand break (DSB) by recombination, pairing with a homologous partner is required. If the sister chromatid is not readily available as a template, a so-called homology search must be initiated. Susan Gasser’s group uses budding yeast to study the mobility of DNA loci within the nucleoplasm.
With the help of quantitative single-particle tracking and high-resolution imaging techniques they found that damaged loci move a lot more than undamaged chromatin regions. However, not only a local but also a global increase in chromatin mobility seems to be necessary to repair the induced damage. This was shown to be dependent on DNA damage checkpoint activation through Mec-1 and downstream INO80 activity. Furthermore, DSBs were preferentially repaired at distinct sites in the nucleus or at nuclear pores, depending on the cell cycle phase.
Spatial separation of DNA repair pathways within heterochromatin
Evi Soutoglou, IGBMC, Straßbourg, France
In line with Susan Gasser’s talk, the Soutoglou group set out to study the spatial impact on DNA repair in different compartments of mammalian cell nuclei. The choice between DNA repair pathways (e.g. homologous recombination or non-homologous end joining) is often crucial to maintain genome stability. Distinct pathways have been reported to preferentially take place at the nuclear pore or the periphery, suggesting that DNA lesion sites might relocate within the nucleus prior to DNA repair. The Soutoglou group elegantly used the popular CRISPR/Cas9 system to selectively induce DNA double-strand breaks in different nuclear environments and follow their corresponding fates. The observed chromatin dynamics were complemented with mutant analyses and overexpression of modulating factors to determine which repair mechanism takes place at each site. DNA repair organization seems to be dependent not only on chromatin structure and location but also the availability of single-stranded DNA and the cell cycle state at the moment of DNA damage.
These are just a few of the excellent talks presented at the third annual IMB conference. In addition to the excellent talks, the conference also included a sightseeing boat excursion with dinner on board on the beautiful Rhine River further contributing to an enjoyable, relaxed and stimulating atmosphere.
** Thanks to Lisa Schmunk from the University of Freiburg for providing this conference coverage.